Improved estimation of ischemic burden with cardiac MRI Summary: Coronary artery disease (CAD) is a major healthcare problem that affects over 20 million Americans and costs our nation an estimated $82.8 billion each year. Myocardial perfusion imaging is a proven tool to detect and characterize CAD. Perfusion defect size, also termed ischemic burden, is a promising biomarker not only for triaging patients for catheterization but also in longitudinal studies to determine the efficacy of therapy and to predict future cardiac events. While these and most other studies to date used Single Photon Emission Computed Tomography (SPECT) imaging, Magnetic Resonance Imaging (MRI) may be more suitable for estimating ischemic burden. MRI offers superior in-plane spatial resolution than SPECT without the ionizing radiation and in a fraction of the total exam time. MRI also offers a gold standard Late Gadolinium Enhancement (LGE) imaging method for identifying infarcted myocardial tissue. By subtracting the infarcted tissue size from the perfusion defect size computed using MR stress perfusion images, a more accurate estimation of ischemic burden is possible. However, the resolution and slice coverage obtained with standard perfusion MRI is limited and often involves skipping large regions of myocardial tissue between the slices acquired. The inevitable tradeoff between having complete slice coverage and preserving high temporal resolution potentially leads to missed regions of perfusion deficit. The tradeoff problem is exacerbated when the ECG gating signal is poor and when imaging patients with irregular heart rate, for example in patients with atrial fibrillation, a common condition in patients with CAD. Ungated cardiac perfusion MRI is a recently popular approach that mitigates this tradeoff by continuously acquiring data with very high temporal resolution irrespective of the ECG signal. Poor or inconsistent ECG gating can also affect LGE imaging requiring several additional breath holds and long acquisition times with conventional segmented acquisitions. Inconsistent R-R interval between the inversion pulses leads to incomplete recovery of longitudinal magnetization and improper nulling of the healthy tissue in LGE imaging. Ungated free-breathing acquisitions are also simpler than conventional acquisitions which impose breath-holding and ECG gating signal requirements. A simpler and more robust protocol can lead to wider adoption of cardiac MRI techniques for CAD management. Specific aims are (1) To develop novel simultaneous multi-slice techniques with advanced reconstruction methods that are robust to the motion. (2) To rigorously compare the new MR methods with existing MR technology. (3) To validate the new framework by comparing ischemic burden computed using SPECT in a pilot study. Our team has complementary experience to successfully execute all aspects of this project. The success of our study will deliver a game-changing technology that addresses critical barriers to computing ischemic burden and more accurately characterizes CAD using MRI, even for patients with arrhythmias allowing for more widespread use of radiation-free cardiac perfusion and LGE-MRI. !